Prostatic needle biopsies showing high-grade cancer typically contain abundant tumor. However, the histologic features of a minute focus of high-grade cancer on biopsy have not been well studied. A total of 100 cases with a single minute focus (< or = 1 mm) of Gleason score (GS) 8-10 adenocarcinoma were identified from a large consultative service, systematically studied, and compared with the submitting institutions' provisional diagnoses. The mean size of the minute foci was 0.52 mm. A total of 29 cases were GS 8 with cribriform glands (n = 15), poorly formed glands (n = 6), fused glands (n = 3), or combinations of the three (n = 5). A total of 38 cases were GS 9, with: single cells and poorly formed glands (n = 20); extremely poorly formed glands/borderline pattern 4/5 (n = 4); combinations of single cells, sheets, or nests of cells mixed with glands that were either poorly formed, cribriform, or fused (n = 14). A total of 33 cases were GS 10, with single cells (n = 23), single cells with nests (n = 9), or single cells with sheets of cells (n = 1). A total of 69 foci were located adjacent to benign glands, while 31 were on the edge or at the end of the core. Perineural invasion was observed in only 1 case. A total of 72 cases showed moderate to abundant amphophilic cytoplasm. Frequent prominent nucleoli (n = 11), mitoses (n = 8), and apoptotic bodies (n = 11) were infrequently observed. Of 59 cases with known provisional diagnoses, 46 were diagnosed as atypical (n = 37) or as cancer with GS < 8 (n = 9). Pathologists must be attuned to the complex and varied architectural patterns seen in low-volume, high-grade prostate cancer as its diagnosis has both important prognostic and therapeutic implications.